In the area of animal husbandry, antimicrobials, including antibacterials, are used routinely for prophylaxis, chemotherapy and growth promotion. Animals receiving antibiotics in their feed, gain four to five percent more body weight than animals that do not receive antibiotics. They are important for sustainable livestock production ad for the control of animal infections that could be passed on to humans. However, microbiological and clinical evidence is mounting that resistant bacteria or resistance determinants might be passed from animals to humans, resulting in human infections that are more difficult to treat. With a marked increase in the prevalence and distribution of antimicrobial-resistant infections in hospitals and the community the question has been raised as to how this escalation of resistance could have been influenced by the use of antimicrobials in livestock production.
Antimicrobials are used extensively in livestock, fish and plant production. Most are administered to livestock animals in subtherapeutic doses as growth promoters which boost the utilization of the genetic potential for growth of pigs and poultry, improve feed conversion and reduce waste production output from intensive livestock production. They are also used prophylactically to prevent diseases, for example, after commingling of animals from different farms, or among animals raised in crowded conditions with thousands of animals living under confinement on a single premises.
Antimicrobial use leads to the selection of resistant forms of bacteria in the ecosystem of use. Low level, long-term exposure to antimicrobials may have a greater selective potential than short-term, full-dose therapeutic use because full doses are more likely to kill all of the targeted bacteria in the host, making it less likely that resistant bacteria will emerge. Adverse consequences of selecting resistant bacteria include an increase in the prevalence of resistant bacteria in animals, causing diseases that won't respond to known antimicrobials; the transfer of resistant pathogens to humans via direct contact with animals, or through the consumption of contaminated food or water; the transfer of resistance genes to human bacteria; an increase in the incidence of human infection caused by resistant pathogens; and potential therapeutic failures in animals and humans.
Antibiotic resistance that arises in animal husbandry affects such zoonotic pathogens as Salmonella serovars and Campylobacter, both of which are associated with diarrheal diseases, and human and animal commensals such as Escherichia coli and enterococci. Because the human and animal microbial ecosystems are inextricably intertwined, microbial antibiotic resistance readily crosses boundaries so that antibiotics given to animals and closely related antibiotic compounds used in human therapy have been exerting selective pressure on their target bacteria for decades.
Specifically, the introduction of fluorquinolones for use in poultry caused a dramatic rise in the prevalence of fluoroquinolone-resistant Campylobacter jejuni isolated in live poultry, poultry meat and from infected humans. The use of avoparcin as a growth-promoting feed additive for pigs and poultry has contributed to the reservoir of transferable resistance genes to glycopeptides, including vancomycin, in the commensal enterococci of animals. Multiresistant Escherichia coli have been selected by use of broad spectrum antimicrobials in both livestock and humans.
The problems caused by the prolific use of a wide variety of antimicrobials in animal husbandry is a driving force for the development of antibiotic resistance in certain pathogenic bacterial species. The problems of resistance reach beyond the country of origin because meat products are traded worldwide.
The present invention is therefore directed to a nontoxic, non-antimicrobial agent that can replace or supplement the use of antibiotics in the animal husbandry of livestock animals to increase health and general well-being, productivity, feed efficiency and weight gain. The present invention is also directed to such an agent that increases the vitality of livestock animals as is indicated by their ability to withstand environmental stressors such as wide variations in temperature, food deprivation which can occur under crowded condition, and exposure to pathogenic bacteria and viruses.